Advances in anti-BRAF therapies for lung cancer

Roviello, Giandomenico; D’Angelo, Alberto; Sirico, Marianna; Pittacolo, Matteo; Conter, Felipe Umpierre; Sobhani, Navid

doi:10.1007/s10637-021-01068-8

Cited by 28 publications

(12 citation statements)

References 82 publications

(91 reference statements)

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“…According to the guidelines for the treatment of NSCLC, identification of activating mutations of EGFR and ALK is recommended [ 2 ]. According to the literature, 10–13% of Caucasian patients with adenocarcinoma (which represents the most part of non-squamous NSCLC) presents an EGFR activating mutation, 2–7% rearrangements of ALK and 1–4% BRAF mutations [ 2 , 22 ]. In line with these data, about 10% of patients with non-squamous NSCLC in our study cohort were treated with target therapies.…”

Section: Discussionmentioning

confidence: 99%

First-Line Pharmacotherapies and Survival among Patients Diagnosed with Non-Resectable NSCLC: A Real-Life Setting Study with Gender Prospective

Spini

Gini

Rosellini

et al. 2021

Cancers

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(1) Purpose: To describe first-line pharmacotherapy and overall survival in non-resectable non-small cell lung cancer (nrNSCLC) patients by gender. (2) Methods: Incident cases of nrNSCLC recorded between 2009 and 2019 (cohort entry) in the pathology registry of the regional administrative healthcare database of Tuscany were identified. Records of antineoplastic therapies delivered up to 4 months following cohort entry were classified as chemotherapy, target therapies, immunotherapies, and undefined monoclonal antibodies. First-line treatment and survival of patients receiving drug treatment was described. Analyses were stratified according to histology, gender, and cohort entry year. (3) Results: 4393 incident cases of nrNSCLC were included. Women with non-squamous-NSCLC received target-therapy more frequently than men (14.9% vs. 6.5%). Immunotherapy incidence of use varied between 3.8% (2017) and 9.1% (2019). The 2-year survival rate increased over time: for non-squamous-NSCLC, it was 22.3% (2009–2011) and 30.6% (2018–2019), while for squamous-NSCLC, it was 13.5% and 22.5%, respectively. After multivariate analysis, a low reduction in mortality risk in 2018–2019 vs. 2009–2011 was found (non-squamous: HR: 0.95 CI95%: 0.92–0.98; squamous: HR: 0.94 CI95%: 0.90–0.98). Among non-squamous NSCLC, median survival was longer in women than in men (389 vs. 276 days). (4) Conclusion: In light of sex-related biomolecular differences, among non-squamous NSCLC, women received target-therapy more frequently than men. Survival seemed to slightly improve over the study period for both histologies, despite a poor reduction in mortality risk was still observed.

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Section: Discussionmentioning

confidence: 99%

First-Line Pharmacotherapies and Survival among Patients Diagnosed with Non-Resectable NSCLC: A Real-Life Setting Study with Gender Prospective

Spini

Gini

Rosellini

et al. 2021

Cancers

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“…When we constructed PPI networks of molecules elevated by cDNA microarray and proteomic analysis, both networks were similar ( Supplementary Figures S1 and S2 ). Although there are many reports on the induction of cancer cell differentiation and growth inhibition [ 47 , 48 ], there are almost no reports on the involvement of HBp17. It was reported that FLG expression increases in HBp17 -KO mice [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Heparin-Binding Protein 17/Fibroblast Growth Factor-Binding Protein-1 Knockout Inhibits Proliferation and Induces Differentiation of Squamous Cell Carcinoma Cells

Shintani

Higaki

Okamoto

2021

Cancers

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Heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1) has been observed to induce the tumorigenic potential of epithelial cells and is highly expressed in oral cancer cell lines and tissues. It is also recognized as a pro-angiogenic molecule because of its interaction with fibroblast growth factor (FGF)-2. In this study, we examined the functional role of HBp17/FGFBP-1 in A431 and HO-1-N-1 cells. Originally, HBp17/FGFBP-1 was purified from A431 cell-conditioned media based on its capacity to bind to FGF-1 and FGF-2. We isolated and established HBp17/FGFBP-1-knockout (KO)-A431 and KO-HO-1-N-1 cell lines using the clusters of regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) gene editing technology. The amount of FGF-2 secreted into conditioned medium decreased for A431-HBp17-KO and HO-1-N-1-HBp17-KO cells compared to their WT counterparts. Functional assessment showed that HBp17/FGFBP-1 KO inhibited cell proliferation, colony formation, and cell motility in vitro. It also inhibited tumor growth in vivo compared to controls, which confirmed the significant difference in growth in vitro between HBp17-KO cells and wild-type (WT) cells, indicating that HBp17/FGFBP-1 is a potent therapeutic target in squamous cell carcinomas (SCC) and oral squamous cell carcinomas (OSCC). In addition, complementary DNA/protein expression analysis followed by Gene Ontology and protein–protein interaction (PPI) analysis using the Database for Visualization and Integrated Discovery and Search Tool for the Retrieval of Interacting Genes/Proteins showed that both gene and protein expression related to epidermal development, cornification, and keratinization were upregulated in A431-HBp17-KO and HO-1-N-1-KO cells. This is the first discovery of a novel role of HBp17/FGFBP-1 that regulates SCC and OSCC cell differentiation.

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“…Given the favorable responses shown in patients with other aggressive neoplasms such as melanoma, the use of different targeted therapies has been studied, with the V600E mutation being the most frequent in lung adenocarcinoma. Patients with BRAF mutations tend to have a better prognosis than those without mutations, as this conditions a better response to immunotherapeutic treatment with dabrafenib and trametinib ( 53 ). Another type of molecular alteration described are alterations in tropomyosin receptor kinases, which are present in <1% of adenocarcinomas that are candidates for treatment with larotrectinib and entrectatinib, reaching response rates of up to 80% and a median survival of 90 months ( 54 ).…”

Section: Molecular and Histological Markers In Lung Cancermentioning

confidence: 99%

Exploring histopathological and serum biomarkers in lung adenocarcinoma: Clinical applications and translational opportunities (Review)

et al. 2022

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Lung cancer represents one of the most common neoplasms and the main cause of cancer-associated death worldwide. Its relationship with different risk factors such as tobacco, which is its main etiological factor, has been clearly established and despite the numerous advances achieved in the diagnosis, treatment and follow-up of these patients, the life expectancy of these patients is notably limited. Furthermore, its treatment is not exempt from comorbidities and frequently it neither provides optimal control of the disease nor improve the quality of life of these patients. Despite the possibility of performing screening tests in patients at risk, their implementation in daily clinical practice is complex and most of them are diagnosed at an advanced stage of their disease where systemic radiotherapy or chemotherapy treatments slightly improve their prognosis. Lung adenocarcinoma is the most representative type of lung cancer, with specific epidemiological, molecular and clinical features. Thus, a growing number of studies are being conducted to find potential therapeutic targets based on the study of different molecular pathways, improving the outcome for these patients. In addition, a broad spectrum of serological, immunohistochemical and genetic markers are being evaluated for use in the screening and follow-up of these patients in daily clinical practice, but unlike for other tumors, they are currently not implemented in the early diagnosis of the disease. Therefore, the aim of the present review was to summarize the main advances that have occurred in the development of serological and histological markers and their therapeutic implications in patients diagnosed with lung adenocarcinoma, explaining the limitations that have been observed and analyzing the future perspectives in the clinical management of this disease. Contents 1. Introduction 2. Molecular and histological markers in lung cancer 3. Serological markers 4. Circulating tumor cells 5. MicroRNAs 6. Conclusions

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Advances in anti-BRAF therapies for lung cancer

Cited by 28 publications

References 82 publications

First-Line Pharmacotherapies and Survival among Patients Diagnosed with Non-Resectable NSCLC: A Real-Life Setting Study with Gender Prospective

First-Line Pharmacotherapies and Survival among Patients Diagnosed with Non-Resectable NSCLC: A Real-Life Setting Study with Gender Prospective

Heparin-Binding Protein 17/Fibroblast Growth Factor-Binding Protein-1 Knockout Inhibits Proliferation and Induces Differentiation of Squamous Cell Carcinoma Cells

Exploring histopathological and serum biomarkers in lung adenocarcinoma: Clinical applications and translational opportunities (Review)

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